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Primates With Donor Eggs' Mitochondria: Breakthrough Could Help Prevent Some Maternally-based Diseases

Date:

August 27, 2009

Source:

Oregon Health & Science University

Summary:

Researchers believe they have developed one of the first forms of genetic therapy -- a therapy aimed at preventing serious diseases in unborn children. Specifically, the therapy would combat inherited diseases passed on from mothers to their children through mutated DNA in cell mitochondria.

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A new scientific breakthrough could help break the chain of several maternally-based diseases passed from generation to generation. The technique has successfully resulted in the birth of twin monkeys named "Mito" and "Tracker," the world's first animals derived by a fertility method called spindle transfer.

Researchers at Oregon Health & Science University’s Oregon National Primate Research Center (ONPRC) believe they have developed one of the first forms of genetic therapy – a therapy aimed at preventing serious diseases in unborn children. Specifically, the therapy would combat inherited diseases passed on from mothers to their children through mutated DNA in cell mitochondria.

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The research is published in the Aug. 26 advance online edition of the journal Nature and will appear in a print edition of the journal at a later date.

“We believe this discovery in nonhuman primates can rapidly be translated into human therapies aimed at preventing inherited disorders passed from mothers to their children through the mitochondrial DNA, such as certain forms of cancer, diabetes, infertility, myopathies and neurodegenerative diseases,” explained Shoukhrat Mitalipov, Ph.D., an associate scientist in the Division of Reproductive Sciences at ONPRC, the Oregon Stem Cell Center and the departments of Obstetrics and Gynecology and Molecular & Medical Genetics of Oregon Health & Science University (OHSU). “Currently there are 150 known diseases caused by mutations of the mitochondrial DNA, and approximately 1 out of every 200 children is born with mitochondrial mutations.”

Mitochondria are structures that are found in all cells that provide energy for cell growth and metabolism, which is why they are often called the cell’s “power plant.” The structures produce energy to power each individual cell. Mitochondria also carry their own genetic material.

When an egg cell is fertilized by a sperm cell during reproduction, the embryo almost exclusively inherits the maternal mitochondria present in the egg. This means that any disease-causing genetic mutations that a mother carries in her mitochondrial DNA can be passed on to her offspring. The method developed by OHSU researchers transfers the mother’s chromosomes to a donated egg that has had its chromosomes removed, but which has healthy mitochondria, thereby preventing the disease from being passed on to one’s offspring.

Here is how the OHSU researchers’ method works: Scientists collected groups of unfertilized eggs from two female rhesus macaque monkeys (monkeys A and B). They then removed the chromosomes, which contain the genes found in the cell nucleus, from the eggs of monkey B, and then transplanted the nuclear genes from the eggs of monkey A into the eggs of monkey B. Then the eggs from monkey B, which now contained their own mitochondria but monkey A’s nuclear genes, were fertilized. The fertilized eggs developed into embryos that were implanted in surrogate monkeys.

The initial implantation of two embryos resulted in the birth of healthy twin monkeys, nicknamed “Mito” and “Tracker” (in reference to the procedure used for imaging of mitochondria). These monkeys are the world’s first animals derived by spindle transfer.

Follow-up testing showed that there was little to no trace of cross-animal mitochondrial transfer using this procedure. This demonstrates that the researchers were successful in isolating nuclear genetic material from mitochondrial genetic material during the transfer process.

“In theory, this research has demonstrated that it is possible to use this therapy in mothers carrying mitochondrial DNA diseases so that we can prevent those diseases from being passed on to their offspring,” added Mitalipov. “We believe that with the proper governmental approvals, our work can rapidly be translated into clinical trials for humans, and, eventually, approved therapies.”

“This breakthrough is an excellent example of how OHSU’s research findings can often be rapidly translated into health therapies that benefit residents of our state and the country as a whole,” said Dr. Joe Robertson, M.D., M.B.A., president of OHSU.

The research was funded by the Oregon National Primate Research Center, the Oregon Stem Cell Center; and the National Center for Research Resources and the National Institute of Child Health and Human Development, both components of the National Institutes of Health.

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